The proposed research is designed to gain insights into the structure function relationships in proteins. We have developed a model system in which the protein under study is a murine immunoglobulin, specific for the hapten, pazobenzenearsonate. We are able to isolate in essentially unlimited numbers and essentially unlimited quantities, mutants of a single antibody that have increased their affinity for the hapten. Similarly, we are able to isolate mutants that have lost their reactivity to antigen. Preliminary results employing x-ray crystallographic methods has demonstrated the feasibility of using this technique for structural analysis in this system. We will also employ the techniques of genetic engineering, site- directed mutagenesis and computer assisted model building to produce variants of the immunoglobulin molecule that will serve to verify deductions concerning structural rules for proteins.